Quantitative inhalation bronchial challenge in ragweed hay fevery patients: a comparison with ragweed-allergic asthmatics.

Fourteen ragweed hay fever nonasthmatic patients comparably sensitive to a group of ragweed-allergic asthmatics by skin test and leukocyte histamine release were tested by quantitative inhalation bronchial challenge with ragweed extract. The provocation dose of ragweed extract producing 35% decrease in airway conductance was determined and designated PD35. PD35 values in the hay fever patients were not significantly different from PD35 values in the asthmatic group. These data suggest that carefully performed skin tests may be as diagnostically useful as bronchial challenge in routinely confirming the allergic etiology of seasonal asthma.     

A controlled study of the effectiveness of the Rinkel method of immunotherapy for ragweed pollen hay fever

In a double-blind study, we compared the effects of the Rinkel method of immunotherapy with ragweed pollen extract and placebo on symptoms of ragweed hay fever and immunologic parameters in 24 ragweed-sensitive patients. Each had a skin-test end point by Rinkel serial dilution titration to ragweed pollen extract at 1:312,500 w/v or greater dilution, a 2+ skin test to ragweed AgE at 0.1 μg/ml or greater dilution, and in vitro leukocyte histamine release by ragweed pollen extract. None had had immunotherapy for at least 7 yr. Patients matched on the basis of leukocyte histamine release by ragweed were assigned to two treatment groups (12 patients in each group). One group received ragweed pollen extract, and the other, placebo, both administered by the Rinkel method between June and October, 1978. Treatment doses were derived from skin-test end points. The median maintenance (“optimal dose”) for patients receiving ragweed pollen extract was 0.53 ml of 1:312,500 w/v and the mean cumulative dose of ragweed pollen extract given during the study contained 0.094 μg of ragweed AgE. Symptom-medication scores of all patients rose and fell with ragweed pollen counts. No significant differences were observed in mean daily symptom-medication scores, antiragweed IgG or IgE levels, leukocyte histamine release by ragweed, total IgE levels, or skin-test end-point dilutions with ragweed pollen extract between the group receiving ragweed pollen extract and the group receiving placebo. Despite the absence of specific effect on symptom-medication scores and measured immunologic variates, 10 of the 12 ragweed-treated patients and 10 of the 12 placebo-treated patients were of the opinion that their hay fever symptoms during the ragweed pollen season were less severe in 1978 than in 1977 and that they had been helped by Rinkel method immunotherapy. Under the conditions of the study, Rinkel method immunotherapy with ragweed pollen extract was no more effective than placebo given in an imitation of the Rinkel method.     

The clinical and immunologic specificity of immunotherapy

In order to study the specificity of immunotherapy for respiratory allergy, a group of patients sensitive to both ragweed and grass pollens were selected. From 87 volunteers with a history of both spring and fall hay fever, 42 patients with evidence of strong sensitivity by basophil histamine release to both ragweed pollen and mixed grass pollen extracts were selected for study. On the basis of the histamine release data, the patients were divided into two groups matched for sensitivity to both grass and ragweed pollens. In 1970, May and June symptom diaries showed the two groups to suffer quite similar severity of symptoms during the grass pollination season. One group of patients was started on a preseasonal course of immunotherapy with alum-precipitated aqueous extract of ragweed pollen while the other group received placebos containing histamine. By fall there had been a considerable rise in IgG-blocking antibodies to ragweed in the treated group. Symptom diaries in August and September showed that the treated group showed significantly less severe symptoms than the placebo group. Both groups received booster injections at 2-wk intervals from the fall of 1970 to the fall of 1971. Doses in the treated group were raised to attempt to administer the largest possible dose. Again there was no difference in the symptoms reported by the two groups during the grass pollination season, but an even greater difference emerged between the two groups during the ragweed season. The following year 1972 the same results were obtained. These data demonstrate that treatment with ragweed pollen extracts has little or no effect on grass pollen symptoms and confirm that immunotherapy is clinically as well as immunologically specific. Antibody responses to the second year of high-dosage booster injections was not greater than responses to a comparatively short preseasonal course given the first year.     

Comparison of Rinkel injection therapy with standard immunotherapy

We compared the results of a controlled, double blind study of standard immunotherapy (SIT) in subjects with ragweed hay fever during 1980 with the results of our study of Rinkel injection therapy (RIT) in a group of subjects with ragweed hay fever in 1979. Both groups were of comparable sensitivity. During the 1980 hay fever season in Milwaukee, 20 subjects with atopic rhinitis due to ragweed pollen (eight from the 1979 group treated with RIT) were given SIT (Tr), while 14 matched subjects (eight from the 1979 placebo group) were treated with a histamine placebo (Pl). The same glycerinated aqueous ragweed extract and glycerinated histamine placebo were used in both studies. The mean cumulative dose of ragweed extract in the 1980 study was 5391 PNU (20.1 μg of antigen E [AgE]) as compared with 41.5 PNU (0.16 μg of AgE) in 1979. Results indicated a significantly lower weekly mean symptom score (SxSc) in the Tr group compared with that of the Pl group in 5 of the 6 wk that ragweed pollen was counted in 1980. Weekly mean medication score (MxSc) and physical exanination score (PESc) showed similar but less striking differences. The mean seasonal SxScs, MxScs, and PEScs of the SIT Tr group were significantly lower than those of the Pl group in 1980 as well as those of the RIT Tr group in 1979. The same indices were also significantly lower in 1980 by paired analyses in the subset of eight subjects treated in both years. RAST scores showed a significant decrease in the “after season” means in the Tr group as compared with the Pl group in 1980 but not in 1979 (analysis of covariance). We conclude that SIT is more effective than a placebo or RIT in reducing SxSc, MxSc, and PESc as well as in diminishing postseason RAST values. We cannot recommend therapy as proposed by Dr. H. J. Rinkel for clinical use at this time.     

Diagnostic tests in ragweed hay fever. A comparison of direct skin tests, IgE antibody measurements, and basophil histamine release

In 87 patients with both spring and fall hay fever symptoms the radioallergosorbent test (RAST) technique for specific IgE antibodies to ragweed was compared with basophil histamine release and direct intradermal skin testing by the threshold dilution technique. The three techniques gave good agreement except with the leastsensitive patients, some of whom had a positive skin test but undetectable histamine release or IgE antibodies. Twenty-one patients who were highly sensitive to ragweed as measured by all three techniques were followed without specific immunotherapy. There was significant agreement between the level of positivity of all three tests and the symptom index obtained during the ragweed season. In 14 of the 21 patients there was a significant correlation between daily ragweed pollen counts and daily symptom indexes during the season. On the other hand, among the 16 least-sensitive patients (as judged by histamine release) the correlation between daily ragweed pollen counts and symptom indexes was significant in only 3 patients. Other significant allergens could not be identified in the latter group, and the cause of their symptoms is not clearly identified but appears not to be ragweed. The RAST is a quantitative technique that gives diagnostically useful information in ragweed hay fever, although not significantly different from basophil histamine release or carefully performed skin testing. The convenience to the patient may, however, offer a noticeable advantage.     

A comparative study of the effectiveness of the Rinkel method and the current standard method of immunotherapy for ragweed pollen hay fever

In a double-blind study, we compared the effects of the Rinkel and the current standard methods of immunotherapy with ragweed pollen extract and those of placebo on symptoms of ragweed hay fever and immunologic parameters in 43 patients highly sensitive to ragweed. Each had a skin-test end point by Rinkel serial titration at 1:312,500 w/v or greater dilution, a 2+ skin test to ragweed AgE 0.01 μg/ml, and in vitro histamine release by ragweed pollen extract. None had had immunotherapy for at least 7 yr. Patients were matched on the basis of leukocyte histamine release to ragweed pollen extract and assigned to treatment groups. Fourteen received ragweed pollen extract by the Rinkel method, 14 received placebo, and 15 received ragweed pollen extract by the current standard method weekly between February and October, 1979. Rinkel method doses were derived from skin-test end points and were advanced to 0.5 ml of the end-point dilution; current standard method doses were advanced to the highest tolerated dose. The median maintenance dose for Rinkel method patients was 0.5 ml of 1:1,562,500 w/v (0.001 μg AgE), and for current standard method patients was 0.3 ml of 1:100 w/v (11 μg AgE). An additional unmatched group of nine similar patients received Rinkel method immunotherapy in both 1978 and 1979. Under the conditions of this study, the current standard method of immunotherapy produced a significant decrease in ragweed hay fever symptom-medication scores, increase in antiragweed IgG levels, and decrease in seasonal rise in antiragweed IgE levels in comparison with the effects of either Rinkel method or placebo. The effect of the Rinkel method on these variates was not significantly different from the effects of placebo.     

Rinkel injection therapy: a multicenter controlled study

The American Academy of Allergy sponsored a 2-yr “double blind” multicenter study of the effect of Rinkel injection therapy (RIT) compared with a histamine placebo in subjects with atopic rhinitis. Accumulated data included the symptom, medication, and physical examination scores and specific IgE antibody levels measured by the radioallergosorbent test (RAST). A total of 155 subjects (81 treated, 74 placebo) entered the project from six centers during their respective ragweed, grass, and mountain cedar pollen (from one center) seasons for a total of 11 pollen seasons. The total mean cumulative dose of extract was 18.6 PNU, which is much lower than recommended for standard immunotherapy. With one exception, none of the centers reported a consistent significant difference between the pollen extract-treated and placebo-treated groups in any of the weekly mean scores or the RAST before, during, and after the pollen seasons. For 4 wk after the height of the mountain cedar season the group treated with pollen extract showed a significant decrease in weekly mean symptom and medication scores as compared with the placebo group. The overall comparison of the mean seasonal scores for the entire study, however, showed no significant difference between the treated and placebo groups. We conclude the RIT is no more effective than a histamine placebo in influencing the weekly mean symptom, medication, and physical examination scores or IgE antibody levels.     

Effect of immunotherapy on immunoglobulin E and immunoglobulin G antibodies to ragweed antigens: a six-year prospective study

The effect of immunotherapy with aqueous short ragweed (SRW) extract on IgE and IgG antibodies was tested over a 6 yr period in 47 adults with ragweed hay fever. Sera were collected each year in July and October from 1973 through 1979. In May 1976, 23 patients began immunotherapy with a lyophilized standardized SRW extract. From 1976 through 1979, treated patients received an average total dose of 4.8 × 10³ protein nitrogen units (1039 μg of AgE). IgE antibodies to SRW and ragweed AgE were measured by the radioallergosorbent test (RAST) in antigen excess using allergens bound to Sepharose. Blocking antibodies primarily of the IgG class were measured by RAST interference. In response to inhalation of ragweed pollen, untreated patients showed seasonal rises (July to October) and postseasonal falls (October to July) of IgE antibodies during the entire study period. IgE antibody levels in the untreated patients decreased with time and from 1974 to 1979 fell 41% (p < 0.003) for an average halftime of 6.2 yr. Before immunotherapy, treated patients also showed seasonal rises and postseasonal falls. Treatment with SRW extract in 1976 produced an abrupt increase in IgE and IgG antibodies and a clear-cut suppression of seasonal rises of IgE antibodies without an effect on postseasonal falls through 1978. From 1974 to 1979, IgE antibodies to AgE and SRW decreased more in the immunized group than in the control group, and by 1979 these levels showed a mean fall of 73%. Blocking antibodies increased in the treated patients and reached maximal levels by July 1978. In 1978 and 1979, the levels of IgG blocking antibodies to AgE were inversely related to the IgE antibody levels to AgE. These results indicate that adults with ragweed hay fever show regular seasonal and postseasonal changes in IgE antibodies and that IgE antibodies spontaneously decrease with time. Immunotherapy magnifies these decreases by suppression of the seasonal rises, but it does not affect the postseasonal falls.     

Measurement of the absolute levels of IgE antibodies in patients with ragweed hay fever: Effect of immunotherapy on seasonal changes and relationship to IgG antibodies

The effect of immunotherapy with aqueous ragweed pollen extract on changes in IgE antibody was analyzed in 40 untreated patients with ragweed hay fever and compared to changes in 63 treated patients. Treated patients received cumulative doses prior to and during treatment ranging from 1.4 × 10⁵ to 4.8 × 10⁶ protein nitrogen units (PNU). IgG antibody to ragweed antigen E (AgE) was measured by radioimmunoprecipitation, while IgE antibody to allergens in crude ragweed extract was measured by the radioallergosorbent test (RAST). The RAST procedure was calibrated using a serum whose content of IgE antibody in nanograms per milliliter had been determined by immunoabsorption, and with this method the absolute quantities of IgE antibodies to ragweed allergens could be measured. Control experiments indicated that the IgG antibodies in the sera of the treated patients did not interfere with the measurements of IgE antibodies. The levels of IgE antibody in serum varied from less than 5 ng/ml to approximately 3,000 ng/ml. IgE antibodies decreased from October, 1973, to July, 1974, and rose sharply from July to October, 1974, following the pollination season. In both untreated and treated patient groups the magnitudes of the decreases were related (p < 0.001) to the levels of IgE antibody in October, and the magnitudes of the rises were related to the levels of IgE antibody in July. In the treated patients with IgE antibody less than 71 ng/ml in October, the rate of decrease (October to July) was less than in the untreated patients. Comparison of the rises in IgE antibody from July to October revealed that these were partially suppressed in the treated group (p < 0.001), and this effect was most marked in patients with July levels less than 36 ng/ml. Levels of IgG antibody to AgE in the treated patients were approximately 70-fold greater than in untreated patients and showed little change over the study period. The levels of IgG and IgE antibody in the treated patients were positively correlated (p < 0.001) at all time periods, and patients with high levels of IgG antibody also had greater declines and rises in IgE antibodies. The results indicate that immunotherapy is associated with (1) a reduction in the seasonal decrease in IgE antibody from October to July in patients with the low levels of IgE antibody, (2) a partial suppression of the rises in IgE antibody from July to October, and (3) that both these effects are related to the level of IgE antibody before the change. In many treated patients both IgE and IgG antibodies were low in spite of parenteral administration of ragweed extract. This result is consistent with the view that overall humoral immunologic reactivity to ragweed antigens is reduced in these patients.     

Polymerized whole ragweed: A two-year follow-up of patients treated with an improved method of immunotherapy

We have previously reported, in a 1-yr study, the effectiveness of polymerized ragweed (PRW) as an improved method of immunotherapy for patients suffering from ragweed hay fever. In that study, treatment with PRW was found to be superior to treatment with monomer ragweed extract (MRW) because of the reduced allergenicity of the PRW. The current study is a 2-yr follow-up of nine patients treated with PRW and nine patients treated with MRW. After 1 yr of immunotherapy, both MRW- and PRW-treated patients received 9,000 protein nitrogen units (PNU) and after a second year of maintenance therapy both groups received a cumulative dose of 15,000 PNU. Serum blocking antibody against ragweed antigen E (AgE) was measured periodically during the study. After 1 yr of immunotherapy, blocking antibody in the PRW- and MRW-treated groups was similar with respective means of 1,300 and 1,500 ng AgE bound per milliliter of serum. At the end of 2 yr of therapy, these serum AgE binding activities rose to 2,700 and 4,100, respectively. No significant local or systemic reactions occurred in the PRW-treated group during the year of maintenance therapy. However, large local reactions prevented three of the nine patients treated with MRW from achieving a monthly maintenance schedule. A significant decrease in rhinitis symptoms was noted in both treated groups as compared with the season before immunotherapy and also to a group of patients untreated with immunotherapy during the 1978 ragweed season.     

Local intranasal immunotherapy with high-dose polymerized ragweed extract

Thirty-one ragweed-allergic patients received preseasonal local intranasal immunotherapy (LNIT) with high doses of gluteraldehyde-polymerized ragweed extract (average total dose 544 micrograms antigen E). Minimal side effects were reported during treatment and did not interfere with the dosing schedule. During the ragweed pollen season, LNIT-treated patients had lower symptom scores for sneezing, rhinorrhea and nasal congestion than a comparable group of untreated ragweed-allergic patients. There was no difference in ragweed-induced eye symptoms between the two groups. Secretory ragweed-specific IgA and IgG rose following LNIT treatment. Absolute antibody titers and changes in titers did not correlate with clinical improvement. LNIT with the polymerized ragweed did not block the seasonal rise in serum ragweed-specific IgE. These results suggest that LNIT with high-dose polymerized ragweed extract is a safe, simple and effective form of immunotherapy.     

Inhalation challenge with ragweed pollen in ragweed-sensitive asthmatics

We reexamined the ability of inhaled ragweed pollen to induce bronchoconstriction in ragweed-sensitive asthmatic patients using a turbo-inhaler to administer pollen quantitatively. Adult subjects were selected for study on the basis of fall season asthmatic attacks, positive skin test, histamine release, RAST, and bronchial challenge responses to ragweed extract. Not one of 12 such subjects had any bronchial response to oral inhalation of whole pollen grains even when the dose was increased to 7640 pollen grains (more than the estimated maximum daily exposure in season), whereas nasal challenge by the same method produced brisk hay fever responses without bronchospasm. On the other hand, when the pollen was ground to fragments with a size range of 1 to 8 micrometers, oral inhalation produced a 35% fall in airways conductance in six of seven subjects in doses ranging from 59 to 20,000 pollen grain equivalents. Atropine pretreatment did not modify the response to pollen fragments, making an irritant response unlikely. These data, coupled with earlier observations that no more than a few pollen grains penetrate further than the larynx, raise further questions about the role of whole ragweed pollen in fall asthma in allergic patients. In addition, ragweed-allergic asthmatics appear not to have their symptoms at the time of maximum pollen load in the air. We believe that small-particle allergens other than ragweed pollen should be considered in most cases of fall seasonal asthma.     

The effect of cromolyn sodium powder as a treatment for ragweed pollinosis

The effect of treating ragweed pollinosis with intranasal cromolyn sodium powder was evaluated in 26 patients in a double-blind clinical study. Thirteen matched patient pairs were treated by either nasal insufflation of cromolyn sodium powder, 20 mg three times daily, or by a placebo powder. Patients were monitored for severity of symptoms by means of daily symptom diaries collected weekly throughout the pollen season. Serum samples were obtained in July prior to the ragweed season and following the ragweed season during the first and fourth weeks of October for the determination of ragweed-specific IgE antibody levels by the radioallergosorbent test. A significant reduction in symptom severity was observed in the treated patients with high preseasonal levels of IgE antibody to ragweed. Initially the levels of IgE antibody to ragweed did not differ between the two groups. IgE antibody levels increased in both groups after pollen exposure, but the treated group showed a significantly greater rise in IgE antibody levels. The results suggest that treatment with cromolyn sodium enhanced IgE antibody response to pollen exposure and significantly reduced the severity of hay fever symptoms in patients with high preseasonal levels of IgE antibody to ragweed.     

Measurement of the potency of allergy extracts by their inhibitory capacities in the radioallergosorbent test

The potencies of 11 commercial extracts of short ragweed pollen were analyzed by skin test end point titration and compared to potency as measured in vitro: (1) by the radioallergosorbent test (RAST), (2) by AgE concentrations, and (3) by protein nitrogen determinations (PNU). RAST potency was determined by the capacity of the extract to inhibit the binding of IgE antibody to solid-phase allergen in the first step of the RAST, and it was expressed as the quantity of extract needed for 50 per cent inhibition of binding. Potencies determined by skin testing in 7 patients were strongly related among the various patients in spite of a 1,000-fold difference in the patients' sensitivity to the extracts. Similarly, potency as measured by RAST inhibition showed about a 1,000-fold difference among the extracts, and the RAST potencies were strongly related to potency as measured by skin testing. Purified antigens derived from short ragweed inhibited binding of IgE antibodies, but the slopes of the inhibition curves were significantly less than those produced by crude or partially purified short ragweed. AgE concentration and PNU concentrations also were correlated with skin test potency, but the range of potencies was less than that found by RAST inhibition. Measurement of the potency of extracts by RAST inhibition should prove useful as a general procedure for the standardization of allergy extracts.     

Capacity of purified antigens and whole pollen extracts to release histamine from leukocytes of hay fever patients

Eighty-seven consecutive patients appearing with complaints suggestive of spring and fall hay fever were subjected to basophil histamine release study with 4 antigenic preparations: whole ragweed extract, antigen E of ragweed, mixed grass pollen extract, and Group I antigen of rye grass. Among the 87 patients, 12 failed to release histamine to ragweed extract or antigen E and 16 failed to release histamine to grass extract or Group I. Among the remaining patients 5 reacted to whole ragweed extract but not antigen E and 2 reacted to mixed grass extract but not Group I. The patients with this pattern were all at the lower end of the spectrum of sensitivity for the crude extracts. These data tend to confirm that antigen E and Group I are the antigens of prime importance in the majority of hay fever patients with ragweed and grass pollen sensitivity respectively.     

Clinical and immunologic evaluation of glutaraldehyde-modified, tyrosine-adsorbed short ragweed extract: a double-blind, placebo-controlled trial

Glutaraldehyde-modified, tyrosine-adsorbed ragweed extract (GTR) is a modification of allergen extract to reduce allergenicity but retain immunogenicity. We evaluated the clinical efficacy and immunologic changes associated with the administration of GTR (16,350 protein nitrogen units) or placebo to a group of 100 atopic subjects with ragweed hay fever. The study was carried out in a double-blind, placebo-controlled fashion. Clinical response was measured by daily symptom diaries. physician evaluations, and patient responses. Changes in ragweed-specific IgE and IgG antibody were evaluated with an amplified enzyme-linked immunosorbent assay (alpha-ELISA) and were compared with measurements by RAST and a protein A-binding assay for IgG antibody. Treatment with GTR resulted in a sixfold increase in blocking IgG antibody and a small increase in IgE-specific antibody. No changes occurred in the placebo treated group. Mild immediate local reactions occurred after 74% of injections, and late-onset local reactions occurred after 62% of injections in the treated group. The placebo-treated group experienced immediate or late local reaction after only 12% of injections. There were two mild late-onset urticarial reactions of a generalized nature in the treatment group. The treatment group experienced significantly fewer symptoms than the placebo group throughout the season (p less than 0.02), although the difference was not dramatic. The results showed that GTR could be safely given in five preseasonal injections, with retained immunogenicity but less potential for generalized reactions. GTR is an improved method of allergy immunotherapy with the potential for clinical benefit when used in a brief preseasonal treatment regimen.     

The immune response of patients with ragweed hay fever treated with polymerized ragweed antigens.

This report describes the immune response of patients with ragweed hay fever treated with polymerized ragweed antigens (PRW). Their IgG antibody responses to crude ragweed extract, antigen E, antigen K, and antigen Ra3 were determined by a solid-phase radioimmunoassay. The results indicate that PRW contains an array of clinically important antigens that are available for immunologic processing and result in an immune response in patients treated with this new form of immunotherapy for ragweed hay fever.     

Reactivity of ragweed allergens with IgE antibodies. Analyses by leukocyte histamine release and the radioallergosorbent test and determination of cross-reactivity.

Five distinct proteins with allergenic activity have been isolated from short ragweed pollen. We initially tested three of these, AgE, AgK, and Ra3, for reactivity with IgE antibodies by leukocyte histamine release and by the radioallergosorbent test (RAST). We found highly significant correlations between the reactivities of these allergens by leukocyte histamine release and by the RAST, consistent with the view that both procedures detected comparable allergenic activity. We next tested the allergenic cross-reactivity of all five ragweed allergens. AgE, AgK, Ra3, Ra4, and Ra5, by RAST inhibition. With solid-phase AgE the only nonhomologous inhibitor was AgK, which cross-reacted weakly and required a 140-fold mass excess of AgK compared to AgE. With solid-phase AgK both AgK and AgE produced significant inhibition; AgE was slightly more potent than the homologous AgK, Ra3 and Ra5 were allergenically unique, because only the homologous allergen produced 50% inhibition. Ra4 was weakly inhibited by AgE, Ra3, and Ra5 when these allergens were added in 300- to 5---fold mass excesses; this weak inhibition may represent either cross-reaction or cross-contamination. We found that RAST inhibition could be used as an assay for the individual ragweed allergens and we demonstrated the presence of all of the allergens in a whole ragweed extract. The sensitivity of the RAST inhibition assay ranged from 10 ng to 100 ng for 50% inhibition. Finally, the solid-phase ragweed allergens were used to determine the frequency of elevated IgE antibody levels in 65 patients with ragweed hay fever. Virtually all of the patients reacted with AgE (97%), while 88% reacted with AgK, 51% reacted with Ra3, 28% reacted with Ra4, and 17% reacted with Ra5. These results highlight the usefulness of the RAST as a specific and sensitive tool for immunochemical studies of allergens.     

Bronchoprovocation: effect on priming and desensitization phenomenon in the lung.

Priming, or increased sensitivity to antigen, has not been demonstrated in the lung and could play a role in asthmatic symptomatology during seasonal pollen exposure. It is also an important consideration in the design of any experimental protocol requiring serial bronchoprovocations with antigen. Thirteen patients with a history of asthma symptoms during the pollen season and a positive skin test to ragweed extract were selected. Patients were given bronchial challenge out of season on 4 successive days with stepwise inhalations of antigen, and airways conductance was monitored in the body plethysmograph. Antigen dose-response curves were drawn, and the cumulative dose required for a 35% reduction in specific airway conductance was calculated and designated Provocation Dose (PD35). No regular trend toward either priming or desensitization was noted. The daily changes in antigen sensitivity did not correlate with daily variation of baseline pulmonary function. To determine if there was any priming due to natural exposure to pollen, 9 patients were brought back and rechallenged during the pollen season with no significant increase in bronchial sensitivity to ragweed extract. The PD35 method provides figures useful for comparing dose-response curves and shows a one-log variation from day to day. Any evaluation by bronchial challenge of antigen sensitivity or drug efficacy must take into account such variation.     

Disodium cromoglycate in ragweed-allergic rhinitis.

This study was designed to test the effectiveness of disodium cromoglycate when compared to placebo in a double-blind study in patients with ragweed allergic rhinitis. Patients were selected on the basis of a clinical history and a 4+ reaction to the intradermal injection of water-soluble ragweed, 0.02 c.c. of 500 PNU/c.c. Active agent/placebo groups were selected at random and were on the drug for approximately 8 wk, commencing 1 wk prior to the onset of the ragweed pollen season. Patient response was evaluated using patient diary cards, number of antihistamine tablets taken, and patient interviews. In the Toronto study, of 17 patients on the active drug, 15 were graded as improved, compared to only 6 of 21 placebo-treated patients who were improved. However, in the Hamilton study, results were less impressive. Nonetheless, it appears that intranasal insufflation of disodium cromoglycate was more effective in reducing ragweed hay fever symptoms than placebo.